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Biomedical subjects

C Silverman

Publications and source records attributed to C Silverman.

At least 37 records · Page 2Linked to original sources
PubMed1994

The outcome and techniques of primary and secondary tracheoesophageal puncture.

OBJECTIVES: To evaluate the outcome of primary vs secondary tracheoesophageal puncture (TEP), in particular the effects of preoperative and postoperative radiotherapy on success and complication rates in primary TEPs, and to highlight modified surgical and management techniques. DESIGN: Retrospective study of case series. SETTING: Chevalier Jackson-Norris Center-Department of Otorhinolaryngology and Bronchoesophagology at Temple University Health Sciences Center Hospital, Philadelphia, Pa. PATIENTS: One hundred six consecutive patients underwent primary TEPs and 30 underwent secondary TEPs for voice restoration after laryngectomy for cancer over a period of 8 years with follow-ups ranging from 6 months to 8.5 years. The group given primary TEP also includes 19 patients who received radiation for cure and salvage laryngectomy and 75 who received full-course postoperative radiotherapy. INTERVENTION: Tracheoesophageal puncture and Blom-Singer prosthesis. MAIN OUTCOME MEASURES: Speech measures including (1) voice intensity, (2) pitch of speech, (3) duration of sustained phonation, and (4) rate of speech. RESULTS: A success rate of 93% was achieved in the group of patients given primary TEP regardless of radiotherapy. An 83% success rate was achieved with patients given secondary TEP. There were no major complications related to TEPs. CONCLUSIONS: Primary TEP for patients requiring total laryngectomy is highly recommended since a second operative procedure can be avoided and speech obtained rapidly. Postoperative radiotherapy does not increase the complication rate from TEP.

Adult↗
PubMed1994

Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant.

A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NS1(81), formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines.

Adjuvants, Immunologic↗
PubMed1994

Baby boomers in retirement: what are their prospects?

This Issue Brief examines the baby boomers' retirement income prospects by analyzing trends in the elderly's income and pension participation among workers; examining saving behavior and critically evaluating studies of the adequacy of the boomers' saving; and looking at tenure trends, lump-sum distribution preservation, and changes in Social Security benefits. Since the mid 1970s, the real median income of individuals aged 65 and over has increased 18 percent. Sources of income have shifted, with employment-based pensions increasing and earnings and asset income decreasing as a proportion of income. The boomers' prospects are partly dependent on participation in employment-based retirement plans. After decreases in the sponsorship rates, participation rates, and vesting rates of workers during the 1980s, all three percentages increased during the early 1990s. Data do not support the perception that the U.S. work force is becoming increasingly mobile. Tenure levels for prime age workers in the 1980s and beginning of the 1990s were higher than those of previous decades. Still, in response to competitive pressures, employers may not offer the security of paternalistic benefit packages as in the past. Various studies have reached different conclusions regarding the adequacy of the boomers' financial preparation for retirement. Evidence indicates that boomers, in general, will enjoy a retirement standard of living exceeding that of their parents. It is less clear whether they will maintain a standard of living in retirement comparable to that of their working years. To the extent they are willing to tap housing wealth, they would appear at this early stage to be in good shape. Federal fiscal policy decisions will impact boomers by affecting their disposable income today, and thus their ability to save, as well as the benefits they will receive in retirement through Social Security and Medicare. The boomers are 17 to 35 years away from age 65. Given heterogeneity of the boomers, research is needed to identify what specific groups within the generation are at risk and the magnitude of that risk. Groups that would now appear to be at risk to some degree include non-homeowners, the less educated, the single, and the youngest boomers.

Aged↗
PubMed1993

Induction of cytolytic and antibody responses using Plasmodium falciparum repeatless circumsporozoite protein encapsulated in liposomes.

Plasmodium circumsporozoite (CS) protein-induced antibody and T-cell responses are considered to be important in protective immunity. Since the key repeat determinant of the CS protein may actually restrict the recognition of other potential T- and B-cell sites, a modified Plasmodium falciparum CS protein lacking the central repeat region, RLF, was expressed in Escherichia coli. On purification, RLF was encapsulated into liposomes [L(RLF)] and used for the in vivo induction of cytolytic T lymphocytes (CTL) and antibodies. Immunization of B10.Br (H-2k) mice with L(RLF), but not with RLF, induced CD8+ CTL specific for the P. falciparum CS protein CTL epitope, amino acid residues 368-390. Anti-L(RLF) serum reacted with antigens on intact sporozoites and inhibited sporozoite invasion of hepatoma cells. Antibody specificity studies in New Zealand White rabbits revealed new B-cell sites localized in amino acid residues 84-94, 91-99, 97-106 and 367-375. Although the mechanisms by which liposomes enhance cellular and humoral immune responses remain unknown, liposome-formulated vaccines have been well tolerated in humans; hence, their use in vaccines, when efficacy depends on antibody and CTL responses, may be broadly applicable.

Amino Acid Sequence↗
PubMed1993

Empowerment and self-help agency practice for people with mental disabilities.

During the past 15 years, there has been tremendous growth in the number of self-help groups and agencies for mental health clients. This article examines the self-help perspective in relation to problems with traditional mental health services and the need for client-run services. Self-help agencies see their goal as empowerment on an individual, organizational, and societal level. They strive to accomplish this by helping members obtain needed resources and develop coping skills; providing means of enhancing members' self-concept and lessening the stigma of perceived mental disability; giving members control in the agencies' governance, administration, and service delivery; and furthering member involvement in social policy-making. The goal of this article is not to endorse the self-help perspective but to use it as the basis for raising research questions that will further the mental health practitioner's understanding of this service modality.

Adaptation, Psychological↗
PubMed1992

Liposomal malaria vaccine in humans: a safe and potent adjuvant strategy.

This study describes the safety and immunogenicity of a liposome-based vaccine injected into human subjects. Thirty healthy adult male volunteers were immunized with a liposome-encapsulated recombinant protein (R32NS181) containing epitopes from the repeat region of the circumsporozoite protein of Plasmodium falciparum. This antigen had previously been found to be poorly immunogenic in humans when it was adsorbed with Al(OH)3. In the present study, R32NS181 was encapsulated in liposomes containing monophosphoryl lipid A that were subsequently adsorbed to Al(OH)3. Increasing doses of liposomes containing antigen and monophosphoryl lipid A were used, but the liposomes were always adsorbed to the same dose of Al(OH)3. R32-specific serum IgG antibody responses to liposome-encapsulated R32NS181 were much higher than levels attained previously in humans with R32NS181 adsorbed to Al(OH)3. Geometric mean specific IgG levels after three doses ranged from 14 to 33 micrograms/ml. Sera from volunteers receiving the two highest doses inhibited P. falciparum sporozoite invasion of cultured hepatoma cells by an average of 92%, a result that was again superior to previously reported vaccines. Moderate but acceptable transient local reactogenicity was noted at high doses of the vaccine formulation, but little or no systemic toxicity was seen despite liposomal monophosphoryl lipid A doses up to 2200 micrograms. We conclude that encapsulation of poorly immunogenic circumsporozoite protein repeat peptides in monophosphoryl lipid A-containing liposomes is a successful adjuvant strategy in humans for inducing high levels of specific antibody production.

Adjuvants, Immunologic↗
PubMed1992

Immunogenicity and efficacy trials in Aotus nancymai monkeys with model compounds representing parts of a 75-kD merozoite surface antigen of Plasmodium falciparum.

We tested the ability of a recombinant DNA-encoded fragment (C7Ag) of a Plasmodium falciparum merozoite protein (p75) and of two carrier-free peptide models (28-mer and 76-mer) to stimulate boostable antibody responses in Aotus nancymai monkeys. In addition, we evaluated protection against challenge with the Uganda Palo Alto (FUP) strain of this parasite. The data indicate that C7Ag elicited a strong and boostable IgG antibody response in all the monkeys immunized. However, studies with the peptide models demonstrated that various animals produce antibodies to different portions of this structure. When the post-boost sera from monkeys immunized with C7Ag were analyzed for reactivity against two major portions of C7Ag, most of the antibody response was observed against the disulfide-bonded 76-residue region that forms a conformational immunogenic epitope. In the same sera, antibody levels against the charged helical region modeled with a 28-mer were generally low. Immunization with synthetic peptides revealed that the 76-mer stimulated an antibody response almost as strong as C7Ag, with substantial cross-reactivity against the parasite antigen. The 28-mer evoked a response that was not efficient or uniform, and showed little reactivity with the authentic parasite antigen. Aotus nancymai was shown to be susceptible to infection with the Uganda Palo Alto strain of P. falciparum; however, maximum parasitemia varied markedly in both immunized and control monkeys. Statistical analysis failed to recognize differences in maximum parasitemia between the vaccine and control groups. The variation in maximum parasitemia suggests that the FUP strain in this species of Aotus is a poor model for the detection of differences in efficacy based on maximum parasitemia. This initial study with structures based on parts of the 75-kD merozoite surface antigen of P. falciparum indicated that both the recombinant-produced protein C7 and the 76-mer synthetic peptide, when combined with a Syntex adjuvant formulation, were safe and immunogenic in A. nancymai monkeys. However, the data emphasize the problems of using animal models to evaluate the potential effects of immunogens in humans.

Adjuvants, Immunologic↗
PubMed1991

The CYP2 gene of Saccharomyces cerevisiae encodes a cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase with an N-terminal signal sequence.

Cells of Saccharomyces cerevisiae contain a major cytosolic cyclophilin (Cyp)-related peptidyl-prolyl cis-trans isomerase (PPIase) which is the target for cyclosporin A (CsA) cytotoxicity and which is encoded by the CYP1 gene [Haendler et al., Gene 83 (1989) 39-46]. We recently identified a second Cyp-related gene in yeast, CYP2 [Koser et al., Nucleic Acids Res. 18 (1990) 1643] which predicts a protein with a hydrophobic leader sequence. A sequence lacking 33 codons from the 5'-end of the CYP2 open reading frame was generated by the polymerase chain reaction and engineered for expression in Escherichia coli. The corresponding recombinant truncated protein was purified and found to exhibit PPIase activity which was inhibited by CsA. The CYP2 gene is genetically unlinked to CYP1. As with CYP1, genomic disruption of CYP2 had no effect on haploid cell viability. Disruption of all three of the known yeast PPIase-encoding genes [CYP1, CYP2, and RBP1 for rapamycin-binding protein; Koltin et al., Mol. Cell. Biol. 11 (1991) 1718-1723] in the same haploid cell also resulted in no apparent cellular phenotype, suggesting either that none of these enzymes have an essential function or that additional PPIases can compensate for their specific absence. Whereas cells containing a genomic disruption of CYP1 exhibited a CsA-resistant phenotype, genomic disruption of CYP2 had no effect on CsA sensitivity. This suggests that the CYP1 gene product is the primary cellular target for CsA toxicity in yeast. Since both purified Cyps display CsA sensitivity in vitro, our data suggest that Cyp1 and Cyp2 differ in terms of their cellular function and/or localization.

Amino Acid Isomerases↗
PubMed1991

Immunization of owl monkeys with a recombinant protein containing repeated epitopes of a Plasmodium falciparum glycophorin-binding protein.

A Plasmodium falciparum glycophorin binding protein (GBP-130) has been implicated in protective immunity to malaria. The gene for GBP-130 encodes a protein containing 11 tandemly repetitive 50 amino acid units. We report an immunization trial in Aotus monkeys using a recombinant DNA protein containing three of these 50 amino acid repeats. When administered with aluminum hydroxide, this antigen induced low levels of antibodies that reacted with the recombinant protein by ELISA and with parasite antigens in immunoblot and immunofluorescence assays, but not by immunoprecipitation. When administered with Freund's complete adjuvant, this antigen induced high levels of antibodies that reacted in ELISA, immunoblot, immunofluorescence, and immunoprecipitation assays. Serum from immunized monkeys did not inhibit parasite growth, and protection from intravenous challenge with P. falciparum-infected erythrocytes was not observed in any experimental group. These results suggest that the repetitive region of GBP-130 is not a useful vaccine candidate.

Amino Acid Sequence↗
PubMed1987

Modification of the platelet-binding domain of von Willebrand factor.

Radioiodinated Bolton-Hunter reagent was used at low specific activity to probe for the function and reactivity of amino groups on von Willebrand factor (vWF), a plasma protein involved in platelet responses to damaged endothelial surfaces. The platelet receptor for vWF contains a membrane protein termed glycoprotein Ib. Modification of only one or two amino groups per vWF subunit caused a 50% reduction in the platelet-agglutinating activity of vWF, and a decrease in its ability to bind to platelets. All multimeric forms of vWF are modified. Loss of platelet-agglutinating activity on modification of less than 2% of the amino groups on each vWF subunit suggests that the amino groups in the glycoprotein Ib-binding domain of vWF are both particularly reactive and essential for its function.

Amino Acids↗
PubMed1985

Experimental intravitreal 5-fluorocytosine.

The pyrimidine 5-fluorocytosine is a water soluble agent which may be suitable for intravitreal injection in the treatment of Candida endophthalmitis. Experimental ocular toxicity studies of intravitreal 5-fluorocytosine have been performed in rabbits with the aid of slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and histologic examination. Intravitreal injection of 100 micrograms 5-fluorocytosine produced no detectable ocular injury.

Animals↗
PubMed1983

Response selection and initiation in speeded reactions: a pupillometric analysis.

Three studies are described in which the task-evoked pupillary response is recorded during simple and disjunctive reactions in order to examine its contribution as a measure of the motoric and cognitive aspects of performance in these tasks. In simple reactions a pupillary dilation began about 1.5 sec before the imperative stimulus and peaked about 1 sec after the stimulus. The rate of dilation was inversely related to the interstimulus interval. In disjunctive reactions, both "Go" and "No-Go" responses elicited significant dilations but the No-Go dilation was smaller than the Go dilation. When the response was delayed 2.5 sec after the discrimination stimulus, the dilation to both Go and No-Go responses was much reduced. The pupillary response related to response selection was estimated at 55% of that associated with motor preparation and execution. The probability of responding was found to affect the amplitude of the dilation to No-Go responses but not that to Go responses. The data point to a significant contribution of preparatory motor processing in No-Go reactions and to an overlap between decisional and motoric processing in disjunctive reactions.

Female↗
PubMed1983

High-molecular weight kininogen. A secreted platelet protein.

Human platelets were studied immunochemically to determine if they contain high-molecular weight kininogen. On crossed immunoelectrophoresis with total kininogen antisera (antisera that recognizes both high- and low-molecular weight kininogen) extracts of platelets contained total kininogen antigen. Platelet total kininogen antigen showed complete antigenic identity with plasma total kininogen and displayed the same electrophoretic migration as plasma total kininogen. Using antisera monospecific to high molecular weight kininogen, a competitive enzyme-linked immunosorbent assay (CELISA) was developed to directly measure platelet high-molecular weight kininogen. By CELISA, 27-101 ng of high molecular weight kininogen antigen per 10(8) platelets was quantitated in detergent-soluble lysates of washed human platelets from nine normal donors with a mean level of 60 ng +/- 24/10(8) platelets. Plasma high-molecular weight kininogen, either in the platelet suspending medium or on the surface of the platelets, could only account for 5% of antigen measured in the solubilized platelets. On the CELISA, platelet high-molecular weight kininogen was immunochemically identical to plasma and purified high-molecular weight kininogen. Platelet high-molecular weight kininogen was secreted from platelets after exposure to ionophore A23187 (3-15 microM), collagen (5-150 micrograms/ml), and thrombin (1.6 U/ml). Secreted platelet high-molecular weight kininogen did not become a part of the platelet Triton-insoluble cytoskeleton. On cross immunoelectrophoresis secreted platelet total kininogen antigen had a similar electrophoretic migration to plasma total kininogen. Thus, human platelets contain high-molecular weight kininogen that can be secreted from platelets and that may participate in plasma coagulation reactions.

Adult↗
PubMed1981

Personal usage of medical radiological procedures by radiologists, pathologists, and their families.

The Radiation Registry of Physicians was established to study the biologic effects of prolonged occupational exposure to low levels of ionizing radiation. Questionnaire responses from radiologists and a comparable group of medical specialists, pathologists, provided information about personal and familial exposure to medical radiation. This first report from the 1973 survey of radiologists and pathologists (5077 and 2914 respondents, respectively) shows that a significantly greater percentage of male radiologists, their spouses and their children reported diagnostic and therapeutic radiographic procedures than did male pathologists and their immediate family members. Responses from female physicians show similar relationships but the number of such specialists is too small for meaningful analysis. The exposure differential between radiologists and pathologists suggests that personal medical radiation exposure is an important component of the total x-ray exposure of radiologists.

Data Collection↗